Ostium Primum Atrial Septal Defects

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Updated: Aug 04, 2015
  • Author: Shannon M Rivenes, MD; Chief Editor: Syamasundar Rao Patnana, MD  more...
Overview

Background

An ostium primum atrial septal defect (ASD), as seen in the image below, is located in the most anterior and inferior aspect of the atrial septum. It is the simplest form of atrioventricular (AV) canal or AV septal defect. These defects are often associated with trisomy 21.

Gross pathology specimen viewed from the opened le Gross pathology specimen viewed from the opened left atrium and left ventricle, demonstrating a partial atrioventricular (AV) canal defect. An ostium primum atrial septal defect (ASD) marked by an asterisk (*) is visualized in the inferior aspect of the interatrial septum. An ostium secundum ASD marked by 2 asterisks (**) is also noted. The mitral valve is cleft and the leaflets are thickened and rolled, suggestive of chronic mitral regurgitation. LA = Left atrium; LV = Left ventricle; MV = Mitral valve.

During fetal development, the rudimentary atrium is divided by the septum primum, except for an anterior and inferior space that is the ostium primum. The ostium primum is sealed by fusion of the superior and inferior endocardial cushions around 5 weeks' gestation. Failure to do so results in an ostium primum ASD. The endocardial cushions also contribute to the complete formation of 2 separate AV valves and the inlet interventricular septum. For this reason, ostium primum ASDs commonly are associated with malformations of these structures.

Ostium primum ASDs are most commonly seen with a cleft in the anterior leaflet of the mitral valve, but they may occur in isolation. This is sometimes termed a partial AV canal defect or a partial AV septal defect. In this case, a 5-leaflet AV valve is arranged so that separate right and left components (a tricuspid valve and a mitral valve) are present. The leaflets connect to each other and then adhere to the crest of the interventricular septum. This results in shunting at the atrial level with no ventricular level shunting. Generally, a commissure is observed between the left superior and inferior bridging leaflets because of abnormal fusion of the left tubercle of the superior and inferior cushions, which results in a cleft in the anterior leaflet of the mitral valve.

For patient education resources, see Heart Health Center, as well as Palpitations.

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Pathophysiology

Shunting is predominantly left-to-right in the absence of pulmonary vascular disease or significant right ventricular outflow tract obstruction. This results in volume overload of the right atrium and ventricle and pulmonary overcirculation. If the mitral valve cleft causes significant mitral regurgitation, the left side of the heart also becomes volume overloaded. A left ventricle to right atrium shunt can be present, which further overloads both the right and left heart.

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Etiology

The most common cause of an ostium primum ASD is genetic, associated with trisomy 21. Well-described associations have been reported with Holt-Oram syndromeNoonan syndrome, and Ellis-van Creveld syndrome, among others. In children with normal chromosomes, however, the cause remains unknown. Research into the molecular genetic basis for AV canal and AV septal defects is ongoing.

A study by Rana et al implicated the TBX1 gene in the development of ostium primum ASDs, among other congenital heart defects. According to these investigators, TBX1 -null embryos are impaired in the ability of second heart field cells (multipotent cardiovascular progenitor cells) to be added to the venous pole of the heart, causing ostium primum defects, as well as abnormal development of the dorsal mesenchymal protrusion. [1]

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Epidemiology

United States statistics

Ostium primum ASDs are most commonly associated with Down syndrome (trisomy 21). The incidence of trisomy 21 is 1 per 800 live births, with an increased prevalence observed in children born to older mothers. Note the following:

  • The overall risk of congenital heart disease in patients with Down syndrome is 40-50%. Approximately 65% of those affected have some form of AV septal defect.
  • The inherited risk for children of parents who have an AV septal defect is reported as 9-14%.

Sex- and age-related demographics

The male-to-female ratio is 1:1.

Patients with smaller defects and little or no mitral regurgitation may present at any age with a murmur and/or an abnormal ECG. Those with more severe mitral regurgitation typically present with CHF in the first 1-2 years of life.

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Prognosis

Pediatric patients with small left-to-right shunts and no significant mitral regurgitation who have not undergone surgery are at relatively low risk for complications. In these patients, adult survival is expected, but complications can develop as age advances. Untreated patients with large shunts and/or significant mitral regurgitation are at significant risk of morbidity and mortality. Death, arrhythmia, heart block, refractory heart failure, and advanced pulmonary vascular disease are the most common complications and tend to increase with advancing age. Pulmonary vascular obstructive disease may develop in a subset of patients, with patients with Down syndrome at highest risk. [2]  Prognosis is guarded, and morbidity and mortality are high regardless of therapy.

Surgical repair generally improves life expectancy and alters the natural course of the disease. Long-term outcome of 180 children with ostium primum ASDs from 1982-1996 was assessed by the group at the Hospital for Sick Children in Toronto. [3]  Mean age at repair was 4.6 years, with 23 patients younger than 1 year. Absent or mild symptoms were reported in 145 patients (80%), and severe symptoms or congestive heart failure (CHF) were reported in 34 patients (20%). Follow-up ranged from 2 months to 14.5 years (mean, 6 ± 4.2 y).

Early mortality occurred in 3 patients (1.6%); 2 were infants. [3] Seventeen patients (9%) underwent reoperation (5 infants); 5 patients underwent reoperation for subaortic obstruction, and 12 for left AV valve regurgitation (1 required valve replacement). Actuarial survival was 98% at 10 years with no late deaths. Age and preoperative moderate-to-severe left AV valve regurgitation were predictors of reoperation. Age at repair younger than 1 year was a predictor of death.

A smaller study from the Oregon Health Sciences University assessed 38 consecutive patients aged 3-58 months who underwent correction between 1981 and 1997. Moderate-to-severe mitral regurgitation was present in 45% of patients, and CHF was present in 41%. Closure of the mitral cleft was performed in 92% of patients, and 28% underwent a mitral annuloplasty. The early 30-day mortality was 7.9%. A low incidence of late mitral regurgitation (0.9%) with only one late reoperation was noted on a follow-up lasting 14 years. Eighty-seven percent of patients remained asymptomatic at the last follow-up visit. The study concluded that an aggressive approach to operating at an early age is safe, effective, and yields excellent long-term results.

The conclusions of the Oregon Health Sciences University study were supported by Italian data, which documented 93.5% (±2%) freedom from reoperation at 12.3 years for partial AV canal defects. [4]  Rates were highest in patients with preoperative AV valve regurgitation and a double orifice left AV valve and were statistically lower for patients who had early repair using a bifoliate approach. Results were attributed to the prevention of progressive mitral annular dilatation.

More recently, need for reoperation was reviewed by the Mayo Clinic over a 45-year period (1962-2006). [5]  When reoperation was required, overall late survival was significantly reduced. Ninety six patients underwent reoperation (median interval, 10 y), with a median age at first reoperation of 26 years (range, 10 mo to 71 y). Indications included left atrioventricular valve (LAVV) regurgitation in 67% of patients, subaortic stenosis in 25% of patients, right atrioventricular valve regurgitation in 22% of patients, residual ASD in 11% of patients, and other indications in 6%. Of the 5 early deaths, 3 occurred prior to 1983. No significant difference was noted in 20-year survival after LAVV repair or replacement (69% vs 55%, p = 0.20). At last follow-up (median, 5.2 y; max, 34 y), 81 of 89 late survivors were in New York Heart Association functional class I or II.

The adult experience was reviewed from 1958-1990 at the Mayo Clinic, encompassing 31 patients aged 40-71 years at the time of repair; [6]  23 had repair of the mitral cleft, 2 required mitral valve replacements, and 6 warranted mitral reoperation. Early mortality was 6%; 19 patients were followed for a mean of 14 years, with 14 reporting a sustained postoperative improvement.

Reoperation need for partial versus other forms of ASDs was reviewed by the Pediatric Heart Network. [7]  Two hundred and fifteen patients from 7 North American centers were subtyped as partial (60), transitional (27), complete (120), and canal-type VSD (8). [8] Preoperatively, patients with transitional ASDs had the highest prevalence of moderate or severe LAVV regurgitation (LAVVR, p = 0.01). Annuloplasty was similar among subtypes (p = 0.91). Significant postoperative LAVVR was the most common sequela, with a similar prevalence across centers 6 months after intervention.

Independent predictors of moderate or severe LAVVR at the 6-month follow-up were older age at repair (p = 0.02) but not annuloplasty, subtype, or center (p > 0.4). Annuloplasty failed to decrease the postoperative prevalence of moderate or severe LAVVR at 6 months. After accounting for age at repair, AVSD subtype was not associated with postoperative LAVVR severity or growth failure at 6 months. [8]

Mortality/Morbidity

The presence and degree of associated mitral regurgitation and/or left ventricle to right atrium shunting generally determine symptoms.

Those with either no cleft or a cleft with a mild degree of mitral regurgitation are often asymptomatic. Patients typically are referred for evaluation of a heart murmur in childhood and generally survive well into adulthood. However, adults who have not had the condition repaired often become symptomatic from congestive heart failure (CHF) by age 45 years. Rarely, patients are reported to present in the seventh decade of life. Dyspnea on exertion and fatigue are usual adult complaints. Palpitations secondary to atrial fibrillation or flutter also are common.

Those with more severe mitral regurgitation or left ventricle to right atrium shunting often present in the first 2 years of life. Mortality has been reported to be as high as 30% in this subpopulation in the first year of life.

Although relatively rare, pulmonary vascular obstructive disease may occur in patients with long-standing substantial shunts and significant mitral regurgitation.

Children with trisomy 21 are at higher risk than the general population of developing pulmonary vascular obstructive disease at a younger age. Potential reasons for this include chronic upper airway disease, tonsillar and adenoid hypertrophy, and inadequate alveolarization of the terminal bronchioles, leading to a decreased surface area of the vascular bed.

Complications

Infective endocarditis remains both a preoperative and a postoperative complication. In a study from the Oregon Health Sciences University, the 30-year postoperative incidence of infective endocarditis was 2.8% among patients with ostium primum ASDs. [9]

 

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